Role of SIRT-1 as a Target for Treatment and Prevention of Diabetic Nephropathy: A Review

Abstract

Type-2 diabetes mellitus is a prime factor for the development of Diabetic Nephropathy (DN) that affects the vital organ namely the kidneys, and further alters the functions of the nephron system. DN is nowadays becoming a challenge for scientists towards the world because of its high pervasiveness and complexity of medication. Various risk factors are involved in the initiation of pathogenic DN, which are associated with different pathways against drug activity. Due to this DN becomes an unpredictable query to the researchers. SIRT1 is a silent information regulator factor 2 related enzyme 1 (SIRT1) is nicotinamide adenine dinucleotide (NAD+) dependent deacetylase that functions as an intracellular regulator of transcriptional activity. An activated version of SIRT-1 improves the metabolic diseased conditions associated with other molecular pathways. SIRT1 attenuates diabetic nephropathy in in vitro and in vivo experimental models of diabetes containing Podocytes, Mesangial cells, and Renal proximal tubular cells. SIRT1 shows nephroprotective effects in DN in part through deacetylation of transcription factors i.e., imply in the disease like p53, PTP1B, FOXO, RelA, NF- kβ, STAT-3, and PGC-1α/ PPARγ. It has been shown that some natural products like resveratrol and synthetic compounds are activating the SIRT1, this further involved the cascade pathways to prevent the DN. This review will help regarding the effectiveness of SIRT1as target in the prevention and treatment of DN.

Keywords: Diabetic nephropathy; FoxO1; NAD+; NF-κB pathway; Nrf2 pathway; SIRT1; TAK-1; VEGF; clinical relevance; insulin; oxidative stress; p53; regeneration; transcription factors.